Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection

It has recently been established that both acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are accompanied by a dramatic and selective loss of memory CD4+ T cells predominantly from the mucosal surfaces. The mechanism underlying this depletion of memory CD4+ T cells (that is, T-helper cells specific to previously encountered pathogens) has not been defined. Using highly sensitive, quantitative polymerase chain reaction together with precise sorting of different subsets of CD4+ T cells in various tissues, we show that this loss is explained by a massive infection of memory CD4+ T cells by the virus. Specifically, 30-60% of CD4+ memory T cells throughout the body are infected by SIV at the peak of infection, and most of these infected cells disappear within four days. Furthermore, our data demonstrate that the depletion of memory CD4+ T cells occurs to a similar extent in all tissues. As a consequence, over one-half of all memory CD4+ T cells in SIV-infected macaques are destroyed directly by viral infection during the acute phase-an insult that certainly heralds subsequent immunodeficiency. Our findings point to the importance of reducing the cell-associated viral load during acute infection through therapeutic or vaccination strategies.     

A continuous-wave Raman silicon laser

Achieving optical gain and/or lasing in silicon has been one of the most challenging goals in silicon-based photonics because bulk silicon is an indirect bandgap semiconductor and therefore has a very low light emission efficiency. Recently, stimulated Raman scattering has been used to demonstrate light amplification and lasing in silicon. However, because of the nonlinear optical loss associated with two-photon absorption (TPA)-induced free carrier absorption (FCA), until now lasing has been limited to pulsed operation. Here we demonstrate a continuous-wave silicon Raman laser. Specifically, we show that TPA-induced FCA in silicon can be significantly reduced by introducing a reverse-biased p-i-n diode embedded in a silicon waveguide. The laser cavity is formed by coating the facets of the silicon waveguide with multilayer dielectric films. We have demonstrated stable single mode laser output with side-mode suppression of over 55 dB and linewidth of less than 80 MHz. The lasing threshold depends on the p-i-n reverse bias voltage and the laser wavelength can be tuned by adjusting the wavelength of the pump laser. The demonstration of a continuous-wave silicon laser represents a significant milestone for silicon-based optoelectronic devices.     

现代工程系统演化过程中的技术概念和数学模型：控制、管理、组织

这是一本介绍现代工程系统演化过程中的技术概念和数学模型的书，包括控制、管理、组织等方面内容。二战后工业时代的生产模式使得工程师们开始考虑信息、决策、质量这些抽象的概念。过程技术强调的重点就是实物和信息的计划与控制，随着大生产方式、自动化、控制、通讯与信息技术的改革和发展，工程技术已经成为现代工程的显著特点。     

Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates

Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. Here, we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to immunization with an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) was induced more rapidly than with DNA priming and ADV boosting, but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease, cynomolgus macaques were challenged with Ebola virus after vaccination with ADV-GP and nucleoprotein (NP) vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8(+) T-cell and antibody responses. Even when animals were immunized once with ADV-GP/NP and challenged 28 days later, they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses.     

The Polycomb group protein EZH2 directly controls DNA methylation

The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts-within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)-with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.     

Production of the antimalarial drug precursor artemisinic acid in engineered yeast

Malaria is a global health problem that threatens 300-500 million people and kills more than one million people annually. Disease control is hampered by the occurrence of multi-drug-resistant strains of the malaria parasite Plasmodium falciparum. Synthetic antimalarial drugs and malarial vaccines are currently being developed, but their efficacy against malaria awaits rigorous clinical testing. Artemisinin, a sesquiterpene lactone endoperoxide extracted from Artemisia annua L (family Asteraceae; commonly known as sweet wormwood), is highly effective against multi-drug-resistant Plasmodium spp., but is in short supply and unaffordable to most malaria sufferers. Although total synthesis of artemisinin is difficult and costly, the semi-synthesis of artemisinin or any derivative from microbially sourced artemisinic acid, its immediate precursor, could be a cost-effective, environmentally friendly, high-quality and reliable source of artemisinin. Here we report the engineering of Saccharomyces cerevisiae to produce high titres (up to 100 mg l(-1)) of artemisinic acid using an engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450 monooxygenase (CYP71AV1) from A. annua that performs a three-step oxidation of amorpha-4,11-diene to artemisinic acid. The synthesized artemisinic acid is transported out and retained on the outside of the engineered yeast, meaning that a simple and inexpensive purification process can be used to obtain the desired product. Although the engineered yeast is already capable of producing artemisinic acid at a significantly higher specific productivity than A. annua, yield optimization and industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices.     

Amorphous silica-like carbon dioxide

Among the group IV elements, only carbon forms stable double bonds with oxygen at ambient conditions. At variance with silica and germania, the non-molecular single-bonded crystalline form of carbon dioxide, phase V, only exists at high pressure. The amorphous forms of silica (a-SiO2) and germania (a-GeO2) are well known at ambient conditions; however, the amorphous, non-molecular form of CO2 has so far been described only as a result of first-principles simulations. Here we report the synthesis of an amorphous, silica-like form of carbon dioxide, a-CO2, which we call 'a-carbonia'. The compression of the molecular phase III of CO2 between 40 and 48 GPa at room temperature initiated the transformation to the non-molecular amorphous phase. Infrared spectra measured at temperatures up to 680 K show the progressive formation of C-O single bonds and the simultaneous disappearance of all molecular signatures. Furthermore, state-of-the-art Raman and synchrotron X-ray diffraction measurements on temperature-quenched samples confirm the amorphous character of the material. Comparison with vibrational and diffraction data for a-SiO2 and a-GeO2, as well as with the structure factor calculated for the a-CO2 sample obtained by first-principles molecular dynamics, shows that a-CO2 is structurally homologous to the other group IV dioxide glasses. We therefore conclude that the class of archetypal network-forming disordered systems, including a-SiO2, a-GeO2 and water, must be extended to include a-CO2.     

用于发动机虚拟开发的3D-CFD-CHT方法

为降低开发成本,需要在开发过程中明确几何结构、总成布置及不同燃料对内燃机性能的影响,这其中一种有效的创新性融和分析方法——三维计算流体动力学-热-结构耦合（3D-CFD-CHT）方法已然成为内燃机开发过程中必不可少的工具。该类工具正在被越来越多的制造商用于发动机开发方案筛选及样机原型确定。本文主要介绍一种由斯图加特汽车工程与车辆发动机研究所（FKFS）开发的针对内燃机虚拟开发的3D-CFD仿真工具—QuickSim。该工具通过将较为粗糙的计算网格与自行开发的内燃机模型有效结合,有效减少计算时间,能以较高精度模拟整个发动机的运行。本文以尽可能实现高燃烧效率及低污染排放为目标,展示该工具在不同替代燃料发动机方面的设计优化能力,探讨不同燃料如氢气、甲醇、各类合成燃料及生物燃料对不同发动机几何结构的影响,探讨燃油喷射系统以及点火系统（包括主动和被动预燃室）对发动机的影响。同时,针对甲烷和氢气发动机,讨论稀薄燃烧对减少节流和爆震的影响;总结如何根据任一选定燃料,通过合理的几何结构设计,提高发动机的指示功率。